(1) Field of the Invention
The present invention relates to specific Ti, Al and Nb alloys which are useful for various structures and particularly for biomedical applications, such as for implants in the human or lower mammalian body. In particular, the present invention relates to Ti-15 Al-33Nb and Ti-21 Al-29 Nb alloys for biomedical applications.
(2) Description of the Related Art
Erosive bone diseases, such as osteoporosis, periodontitis, rheumatoid arthritis, hypercalcemia of malignancy and aseptic loosening, are a growing medical problem which can lead to the need for replacement surgery with bone-replacement materials. Such materials must exhibit several characteristics in order to be successful including biocompatibility with near-bone hard and soft tissue, a modulus near that for bone to prevent stress shielding, and a tensile and compressive strength and fracture toughness equal to or greater than that of bone. In addition, the fatigue strength of the material should guarantee a safe operation of the implant during the expected period of use. Due to their excellent specific strength and electrochemical corrosion resistance, in addition to exceptional biocompatibility characteristics (i.e. benign biological responses) among metallic biomaterials, commercially pure titanium (cp-Ti) and α/β type Ti alloys are currently widely used as structural biomaterials for the replacement of hard tissues in devices such as artificial knee joints and dental implants. However, attempts to develop specific Ti—Al—Nb alloys as biocompatible systems have been lacking.
The recent trend in research and development of titanium alloys for biomedical applications is to develop low rigidity β-type titanium alloys composed of non-toxic and non-allergic elements with excellent mechanical properties, especially fatigue resistance, and workability (ASTM designation draft #3. Standard specification for wrought titanium-35 Niobium-7zirconium-5tantalum alloy for surgical implant applications (UNS R58350), Philadelphia, Pa., ASTM, 2000; ASTM designation draft #6, Standard specification for wrought titanium-3aluminum-2.5vanadium alloy seamless tubing for surgical implant applications *UNS R-56320), Philadelphia, Pa., ASTM, 2000; J. A. Davidson, F. S. Georgette, Proceedings of the implant manufacturing and material technology. Society of Manufacturing Engineers, Dearborn, 1987: EM87-122-1-EM87-122-26; and M. Niinomi, Metal Mater. Trans. 33A, (2002) pages 477-486)). New titanium alloys for biomedical applications are now being included in American Society for Testing and Materials (ASTM) standards. For example, β Ti-15 Mo(wt. %) (ASTM designation F2066-01, Standard specification for wrought titanium-15 molybdenum alloy for surgical implant applications, Philadelphia, Pa., ASTM, pages 1605-1608), Ti-35Nb-7Zr-5Ta(wt. %) (ASTM designation draft #3, ibid), and Ti-3Al-2.5V(wt. %) (ASTM designation draft #6, ibid) have been registered or are in the process of being registered in ASTM standards. β-type titanium alloys have been developed in order to obtain low rigidity, which is considered effective for promoting bone healing and remodeling. Although the rigidity of α/β type titanium alloys is less than that of Co—Cr type alloys and stainless steels used for biomedical applications, it is still considerably greater than that of the cortical bone (J. A. Davidson et al. 1987, ibid).
Several investigations have included newer high titanium alloys based on the Ti—Al—Nb system, such as Ti-6Al-7Nb(wt. %) [Ti-10.5Al-3.6Nb(at. %)] where Nb replaces V (M. F. Lopez, J. A. Jimenez, A. Gutierrez, Electrochimica Acta 48 (2003) pages 1395-1401; M. Metikos-Hukovic, E. Tkalcec, A. Kwokal, J. Piljac, Surface and Coatings Technology, 165 (2003), pages 40-50; Z. Chai, T. Shafter, I. Watanabe, M. E. Nunn, T. Okabe, Biomaterials 24 (2003), pages 213-218; D. Iijima, T. Yoneyama, H. Doi, H. Hamanaka, N. Kurosaki, Biomaterials 24 (2003), pages 1519-1524; M. A. Khan, R. L. Williams*, D. R. Williams, Biomaterials 20 (1999), pages 631-637; M. Papakyriacou, H. Mayer, C. Pypen, H. Plenk Jr., and S. Stanzl-Tschegg, International Journal of Fatigue 22 (2000), pages 873-888; M. F. Semlitsch, H. Weber, R. M. Streicher, and R. Schon, Biomaterials (1992), Vol. 13, No. 11, pages 781-788; I. Watanabe, Y. Tanaka, E. Watanabe, and K. Hisatsune, The Journal of Prosthetic Dentistry (2004) Vol. 92 No. 3 pages 278-282; T. Akahori, M. Niinomi, K. Fukunaga, I. Inagaki, Metallurgical and Materials Transactions, 31A (2000), pages 1949-1958; M. Niinomi, Biomaterials 24 (2003), pages 2673-2683; and “Standard Test Methods for Determining Grain Size Designation E 112-88”, American Society for Testing and Materials (ASTM), West Conshohocken, Pa., 1988, pages 228-253)). Substitution of Nb for V is attractive as depending on the concentration of Nb this does not result in degradation of several mechanical properties.
Other prior art is described in:
                Boehlert, C. J., Understanding Microstructure-Property Relationships of Titanium Alloys, Alfred University, New York State College of Ceramics, School of Ceramic Engineering and Materials Science, New York State web site (2002);        Boehlert, C. J., The Effects of Forging and Rolling on Microstructure in O+BCC Ti—Al—Nb Alloys, pages 1-31, (2000) Materials Science and Engineering, A279/1-2;        Boehlert, C. J., Microstructure, Creep, and Tensile behavior of a Ti-12Al-38Nb(at. %)Beta+Orthorhombic Alloy, pages 1-44, (1999); Materials Science and Engineering, A267        Boehlert, C. J., B. S. Majumdar, V. Seetharaman, and D. B. Miracle, Microstructural Evolution in Ti—Al—Nb O+BCC Alloys, pages 1-41, (1999); Metallurgical Transactions         Boehlert, C. J., and D. B. Miracle, Part II. The Creep Behavior of Ti—Al—Nb O+BCC Orthorhombic Alloys, pages 1-40, (1999); Metallurgical Transactions and        Boehlert, C. J., Part III. The Tensile Behavior of Ti—Al—Nb O+BCC Orthorhombic Alloys, Metallurgical Transactions, pages 1-38 (2001); Metallurgical Transactions         
Currently, more than 1.3 million joint replacement surgeries are performed each year worldwide (W. H. Harris: Clin. Orthop. (1995), pages 46-53), and this number is expected to increase considering the increasing age of the population. When an implant fails, revision arthroplasty is required, which has a poorer clinical result and shorter duration of survival than the primary joint replacement (A. D. Hanssen and J. A. Rand: J. Bone Jt. Surg. Am. 70 (1988), pages 491-499). Implant failure frequently occurs as a result of osteolysis which is defined as a decrease in bone volume and is characterized by a two millimeter gap between prosthesis and bone as seen in radiographs from arthroplasty patients. Osteolysis can be explained by wear debris generated from the prosthesis which is phagocytosed by macrophages (at the bone-implant interface), which produce proinflamatory cytokines such as tumor necrosis factor α (TNFα), interleukin-1 (IL-1), and IL-6 (S. M. Horowitz and M. A. Purdon: Calcif. Tissue Int. 57, (1995), pages 301-305; T. T. Glant and J. J. Jacobs: J. Orthop. Res. 12, (1994), pages 720-731; J. Y. Want, B. H. Wicklund, R. B. Gustilo and D. T. Tsukayama: Biomaterials 17 (1996), pages 2233-2240; A. S. Shanbhag, J. J. Jacobs, J. Black, J. O. Galante, and T. T. Glant: J. Orthop. Res. 13 (1995), pages 792-801; T. A. Blaine, P. F. Pollice, R. N. Rosier, P. R. Reynolds, J. E. Puzas, and R. J. O'Keffe: J. Bone Joint Surg. Am. 79 (1997), pages 1519-1528; S. H. Lee, F. R. Brennan, J. J. Jacobs, R. M. Urban, D. R. Ragasa, and T. T. Glant: J. Orthop. Res. 15 (1997), pages 40-49; and A. A. Ragab, R. Van DeMotter, S. A. Lavish, V. W. Goldberg, J. T. Ninomiya, C. R. Carlin and E. M. Greenfield; J. Orthop. Res. 17 (1999), pages 803-809)). Release of these cytokines leads to an inflammatory response characterized by the activation and recruitment of osteoclasts, which resorb bone after differentiation and activation, to the bone/implant interface and the formation of a periprosthetic membrane (S. R. Goldring, A. L. Shiller, M. S. Roelke, C. M. Rourke, D. A. O'Neil, and W. H. Harris: J. Bone Joint Surg. Am. 65 (1983), pages 575-584; S. R. Goldring, J. Jasty, M. S. Roelke, C. M. Rourke, F. R. Bringhurst, and W. H. Harris: Arthritis. Rheum. 29 (1986), pages 836-842; and A. S. Shanbhag, J. J. Jacobs, J. Black, J. O. Galante, and T. T. Glant: J. Arthroplasty 10 (1995), pages 498-506)). Due to several factors discussed elsewhere (Y. Kadoya, P.A. Revell, N. al-Saffar, A. Kobayashi, G. Scott and M. A. Freeman: J. Orthop. Res. 14 (1996), pages 473-482; D. R. Bertolini, G. E. Nedwin, T. S. Bringman, D. D. Smith, and G. R. Mundy: Nature 319 (1986), pages 516-518; C. S. Lader and A. M. Flanagan: Endocrinology 139 (1998), pages 3157-3164; N. al Saffar and P. A. Revell: Br J. Rheumatol. 33 (1994), pages 309-316; T. A. Blaine, R. N. Rosier J. E. Puzas, R. J. Looney, P. R. Reynolds, S. D. Reynolds, and R. J. O'Keefe: J. Bone Joint Surg. Am. 78 (1996), pages 1181-1192; and K. Kobayashi, N. Takahashi, E. Jimi, N. Udagawa, M. Takami, S. Kotake, N. Nakagawa, M. Kinosaki, K. Yamaguchi, N. Shima, H. Yasuda, T. Morinnaga, K. Higashio, T. J. Martin, and T. Suda: J. Exp. Med. 191 (2000), pages 275-286)), TNFα is considered to be one of the critical cytokines involved in wear debris-induced osteolysis. Using an animal model of particle-induced osteolysis in which polymethylmethacrylate (PMMA) or CP Ti particles were implanted onto mouse calvaria (E. M. Schwarz and R. J. O'Keefe: Arthritis Rheum. 41 (1998), S345 and K. D. Merkel, J. M. Erdmann, K. P. McHugh, Y. Abu-Amer, F. P. Ross, and S. L. Teitelbaum: Am. J. Pathol. 154 (1999), pages 203-210)), TNFα signaling has been demonstrated to be critical to the development of the inflammatory osteolytic response to wear debris. Overall, up to 20% of patients with total joint replacement will demonstrate evidence of osteolysis within ten years where wear debris-induced osteolysis is the leading culprit, and this currently does not have a proven drug therapy (Y. H. Kim, J. S. Kim and S. H. Cho: J. Arthroplasty 14 (1999), pages 538-548; D. Fender, W. M. Harper and P. J. Gregg: J. Bone Jt. Surg. Br. 81 (1999), pages 577-581; and J. J. Callaghan, E. E. Forest, J. P. Olejniczak, D. D. Goetz and R. C. Johnston: J. Bone Jt. Surg. Am. 80 (1998), pages 704-414)). Thus prevention of osteolysis and prosthetic implant loosening is clearly desirable, and one means to address this issue is through evaluation and improvement of biomedical implant materials and their interaction with living cell and bone tissue.
Due to their exceptional biocompatibility characteristics, CP Ti and α/β type Ti alloys are currently widely used as structural biomaterials for the replacement of hard tissues in devices such as artificial hip joints and dental implants. In particular, Ti-6Al-4V(wt. %) is widely used because of its excellent biocompatibility and its combination of high specific strength, fracture toughness, fatigue and corrosion resistance, ductility, low density, elastic modulus, and conventional processability. However, V is potentially toxic in elemental form (G. C. McKay, R. Macnair, C. MacDonald, and M. H. Grant: Biomaterials 17 (1996), pages 1339-1344); therefore, other alloying elements are currently being examined. In fact, new Ti alloys, targeted for biomedical applications and void of V, are now being included in American Society for Testing and Materials standards (ASTM designation F2066-01: Standard specification for wrought titanium-15 molybdenum alloy for surgical implant applications, (ASTM, Philadelphia, Pa.: USA (2001), pages 1605-1608 and ASTM designation draft #3. Standard specification for wrought titanium-35nNiobium-7zirconium-5tantalum alloy for surgical implant applications (UNS R58350): (ASTM, Philadelphia, Pa., USA)). The recent trend in research and development of Ti alloys for biomedical applications is to develop low rigidity β-type alloys composed of non-toxic and non-allergic elements with attractive mechanical properties (M. Niinomi: Metall. Mater. Trans. 33A (2002), pages 477-486). In this regard, several authors have been evaluating alloys based on the Ti—Al—Nb system, such as Ti-6Al-7Nb(wt. %) [Ti-10.5Al-3.6Nb(at. %)] (M. F. Lopez, J. A. Jimenez, A. Gutierrez: Electrochimica Acta 48 (2003), pages 1395-1401; M. Metikos-Hukovic, E. Tkalcec, A. Kwokal, J. Piljac: Surface and Coatings Technology 165 (2003), pages 40-50; Z. Cai, T. Shafer, I. Wantanabe, M. E. Nunn, T. Okabe: Biomaterials 24 (2003), pages 213-218; D. Iijima, T. Yoneyama, H. Doi, H. Hamanaka, N. Kurosaki: Biomaterials 24 (2003), pages 1519-1524; M. A. Khan, R. L. Williams, D. F. Williams: Biomaterials 20 (1999), pages 631-637; M. Papakyriacou, H. Mayer, C. Pypen, H. Plank Jr., and S. Stanzl-Tschegg: International Journal of Fatigue 22 (2000), pages 873-888; M. R. Semlitsch, H. Weber, R. M. Streicher, and R. Schon:Biomaterials 13:11 (1992), pages 781-788; I. Watanabe, Y. Tanaka, E. Watanabe, and K. Hisatsune: The Journal of Prosthetic Dentistry 92:3 (2004), pages 278-282 and T. Akahori, M. Niinomi, K. Fukunaga, I. Inagaki: Metallurgical and Materials Transactions 31A (2000), pages 1949-1958)).